Effects of Increased ICAM-1 on Reperfusion Injury and Chronic Graft Vascular Disease

Poston, Robert; Billingham, Margaret E.; Pollard, Jeffrey D.; Hoyt, E. Grant; Robbins, Robert C.

doi:10.1016/s0003-4975(97)00816-3

Cited by 42 publications

(22 citation statements)

References 16 publications

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“…[36][37][38] Consistent with the decrease of TNF-␣ and IFN-␥ production in cardiac allografts, local overexpression of Bcl-2 resulted in the reduced expression of ICAM-1 and VCAM-1. In addition, Huber et al 39 recently reported that increased Bcl-2 expression on T H 2 cells led to the selective survival of T H 2 cells in the mouse viral myocarditis model.…”

Section: Org Frommentioning

confidence: 70%

Cardiomyocyte-specific Bcl-2 overexpression attenuates ischemia-reperfusion injury, immune response during acute rejection, and graft coronary artery disease

Tanaka

Nakae

Terry

et al. 2004

Blood

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After cardiac transplantation, graft damage occurs secondary to ischemia-reperfusion injury and acute rejection. This damage ultimately leads to the development of graft coronary artery disease (GCAD), which limits long-term graft survival. Apoptosis is directly involved in graft injury, contributing to the development of GCAD. To assess the role of the antiapoptotic factor Bcl-2 in the process of GCAD, we transplanted hearts from FVB transgenic mice overexpressing human Bcl-2 under the control of ␣-myosin heavy chain promoter into allogenic C57BL/6 mice. Bcl-2 overexpression led to reduced cytochrome c-mediated caspase-9-dependent cardiomyocyte apoptosis and local inflammation (neutrophil infiltration and proinflammatory cytokine production) in cardiac allografts during ischemia-reperfusion injury and also led to reduced immune responses (inflammatory cell infiltration, production of T H 1 cytokines and chemokines, and expression of adhesion molecules) during acute and chronic rejection without affecting host CD4 ؉ and CD8 ؉ cell responses in the spleen. Thus, local Bcl-2 expression directly contributes to the modulation of local immune responses in allograft rejection, resulting in attenuated GCAD. In conclusion, our findings suggest that the modulation of Bcl-2 expression by pharmacologic up-regulation or gene transfer may be of clinical benefit in the short-and long-term function of cardiac allografts.

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Section: Org Frommentioning

confidence: 70%

Cardiomyocyte-specific Bcl-2 overexpression attenuates ischemia-reperfusion injury, immune response during acute rejection, and graft coronary artery disease

Tanaka

Nakae

Terry

et al. 2004

Blood

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“…Up-regulated expression of ICAM-1 has been documented in cardiac myocytes after allotransplantation (16), and this adhesion molecule may play an important role in mediating host immune cell interactions with the donor tissue (19,20). We therefore tested the ability of our ODN delivery system to modulate expression of ICAM-1 in rat hearts during the posttransplantation period.…”

Section: Resultsmentioning

confidence: 99%

“…Hearts were harvested from adult male Sprague-Dawley or PVG rats (Ϸ300 g) after induction of anesthesia with intraperitoneal ketamine (35 mg/kg)/xylazine (7 mg/kg) as described (16). The aortic root was cannulated just before excision, and the coronary circulation was perfused with either Stanford cardioplegia solution or heparinized saline solution (1 unit/ml).…”

Section: Methodsmentioning

confidence: 99%

“…The hearts were then placed in a small bath of ODN solution at 4°C, and the entire bath was placed in a custom-designed chamber that was subsequently pressurized to 0.5, 1, or 2 atm (1 atm ϭ 101.3 kPa) above ambient pressure. The hearts were then transplanted heterotopically into the abdominal aorta and vena cava of Sprague-Dawley (isograft) or ACI (allograft) recipients as described (16). The recipients were monitored postoperatively, and beating of the donor heart was confirmed by manual palpation until the time of harvest.…”

Section: Methodsmentioning

confidence: 99%

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Pressure-mediated oligonucleotide transfection of rat and human cardiovascular tissues

Hutchinson

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

118

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The application of gene therapy to human disease is currently restricted by the relatively low efficiency and potential hazards of methods of oligonucleotide or gene delivery. Antisense or transcription factor decoy oligonucleotides have been shown to be effective at altering gene expression in cell culture expreriments, but their in vivo application is limited by the efficiency of cellular delivery, the intracellular stability of the compounds, and their duration of activity. We report herein the development of a highly efficient method for naked oligodeoxynucleotide (ODN) transfection into cardiovascular tissues by using controlled, nondistending pressure without the use of viral vectors, lipid formulations, or exposure to other adjunctive, potentially hazardous substances. In this study, we have documented the ability of ex vivo, pressure-mediated transfection to achieve nuclear localization of fluorescent (FITC)-labeled ODN in approximately 90% and 50% of cells in intact human saphenous vein and rat myocardium, respectively. We have further documented that pressure-mediated delivery of antisense ODN can functionally inhibit target gene expression in both of these tissues in a sequence-specific manner at the mRNA and protein levels. This oligonucleotide transfection system may represent a safe means of achieving the intraoperative genetic engineering of failure-resistant human bypass grafts and may provide an avenue for the genetic manipultation of cardiac allograft rejection, allograft vasculopathy, or other transplant diseases.

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“…23 In addition, treatment with anti-ICAM-1 antibody has been shown to inhibit GCAD in rats. 24 The diseased graft shows abundant ICAM-1, especially on the endothelial surface. 22 These adhesion molecules may facilitate transmigration of inflammatory and immune cells to the graft and contribute to ischemia-reperfusion injury as well as GCAD.…”

Section: Tanaka Et Al Effects Of Superoxide Dismutase 1 On Cardiac Grmentioning

confidence: 99%

Overexpression of Human Copper/Zinc Superoxide Dismutase (SOD1) Suppresses Ischemia–Reperfusion Injury and Subsequent Development of Graft Coronary Artery Disease in Murine Cardiac Grafts

et al. 2004

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Background-Ischemia-reperfusion injury is an important risk factor for graft coronary artery disease (GCAD). We hypothesized that overexpression of SOD1 in donor hearts would suppress ischemia-reperfusion injury and thereby reduce GCAD. Methods and Results-In one series, donor hearts of C57BL/6 (H-2 b ) transgenic mice overexpressing human SOD1 or C57BL/6 wild-type mice were heterotopically transplanted into C57BL/6 recipients and procured after 4 hours of reperfusion (nϭ6 each). Superoxide, TNF-␣, and MCP-1/CCL2 production were significantly reduced in the SOD1 transgenic donor heart recipients, and graft injury determined by serum CPK-MB levels was significantly decreased. Cardiomyocyte apoptosis and caspase-3 and caspase-9 activities were significantly decreased in these recipients; caspase-8 activity was unchanged. Fas ligand but not Fas expression was also reduced. In a second series, transgenic and wild-type hearts were transplanted into C-H-2 bm12 KhEg (H-2 bm12 ) recipients, and then procured on day 56 (nϭ7 each). Cardiac graft beating was significantly better in the SOD1 transgenic donor heart recipients on days 28, 42, and 56 (but not day 14). Significant reduction in luminal narrowing, the intima/media ratio, and the percentage of diseased vessels was seen in the SOD1 transgenic donor heart recipients, and MCP-1/CCL2, ICAM-1, and VCAM-1 production were significantly reduced. Conclusions-Overexpression of SOD1 attenuates both apoptosis and the inflammatory response during ischemiareperfusion injury and therefore mitigates against the subsequent development of GCAD.

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Effects of Increased ICAM-1 on Reperfusion Injury and Chronic Graft Vascular Disease

Cited by 42 publications

References 16 publications

Cardiomyocyte-specific Bcl-2 overexpression attenuates ischemia-reperfusion injury, immune response during acute rejection, and graft coronary artery disease

Cardiomyocyte-specific Bcl-2 overexpression attenuates ischemia-reperfusion injury, immune response during acute rejection, and graft coronary artery disease

Pressure-mediated oligonucleotide transfection of rat and human cardiovascular tissues

Overexpression of Human Copper/Zinc Superoxide Dismutase (SOD1) Suppresses Ischemia–Reperfusion Injury and Subsequent Development of Graft Coronary Artery Disease in Murine Cardiac Grafts

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